Aqueous suspensions often have problems such as difficulty in redispersion due to aggregation of drug particles, formation of macro crystals from suspended particles or formation of secondary particles from deposited particles, any of which could take place during long-term storage or when they are exposed to temporary heating or fluctuation of temperature/humidity. In addition, some types of suspended particles adhere to or get adsorbed by the walls of a plastic container and could thus cause a problem of unstable concentration of the drug contained in the aqueous suspensions.
To address these problems, measures have been taken in order to prevent formation of secondary particles by blocking sedimentation by reducing the size of the particles in suspension and increasing the viscosity of the dispersion medium with a water-soluble macromolecular compound, or to prevent aggregation of particles in the suspension by increasing the size of the particles in the suspension and thereby expanding the space between deposited particles. However, while it is not possible to completely prevent sedimentation of suspended particles by reducing the size of the particles in the suspension and increasing the viscosity of the dispersion medium, this measure could cause a problem by making it more difficult to redisperse particles which are once deposited from the suspension. On the other hand, increasing of the size of particles in the suspension would cause problems such as foreign body sensation upon application or clogging of a container nozzle or a syringe needle.
In this situation, it is disclosed in Japanese Patent Application Publication H8-295622 that an aqueous suspension with good redispersibility can be obtained by addition of an ionic macromolecular compound such as carboxyvinyl polymer or carboxymethylcellulose and a metal cation such as sodium or potassium ion, and adjusting the viscosity to 100 cP. This method, however, cannot be used when high levels of viscosity is desired for improvement of the retention of a drug, because the redispersibility in this method is acquired by its low viscosity of 100 cP.
On the other hand, it is disclosed in EP0995435A1 (WO 98/51281) that an aqueous suspension with good redispersibility is obtained by addition of a water-soluble macromolecular compound within a concentration range from the concentration at which the surface tension of the aqueous suspension begins to decrease up to the concentration at which the reduction in the surface tension ceases. As it employs low concentrations of an aqueous macromolecular compound, this method cannot be used, either, when addition of higher concentrations of the macromolecular compound is needed for other reasons, e.g., for improvement of the retention of a drug.
Thus, there have been needs for an aqueous suspension with good redispersibility irrespective of its viscosity or of the amount of suspending and thickening agents such as water-soluble macromolecular compounds.